Thread by @ManuelPeitsch

1. This is a “20 pt mini review” of the scientific facts that show the harm reduction potential of electronic nicotine delivery products (ENDP). These facts are consistent across studies and coherent along the causal chain of events linking smoking to disease (CELSD) (see Figs).

2. Let’s focus on COPD, and start from the last event: “population harm”. Recent publications have shown that since the market introduction of heated tobacco products in Japan, cigarettes sales have started to decline more sharply than ever before (PMID: 31209129, 32443663). …

3. … and that this drop in cigarette consumption is in large part due to smokers switching to heated tobacco products (HTP) (Figure 1 in PMID: 32443663). Question: can we already see an effect of this change in tobacco product use prevalence on COPD?

4. Indeed, this change in product use prevalence correlates with a decreased rate of hospitalization due to COPD exacerbations, as explained here:

https://twitter.com/PMIScience/status/1375387101244616704?s=20

. Why?

5. Because switching to THS led to a reduction in the rate of COPD exacerbations, improvement of CAT score and 6-min walk distance among COPD patients (event: “disease”), while these parameters were not changed in those who continued to smoke cigarettes (PMID: 33754228). Why?

6. Because switching from cigarette smoking to ENDP use improves mucociliary clearance similarly to cessation: medrxiv.org/content/10.110…. For more references and details see:

https://twitter.com/ManuelPeitsch/status/1346458229304418313?s=20

7. Also because switching from cigarette smoking to THS use improves FEV1, especially in those who switched completely (PMID: 31270101) and in mild to moderate COPD subjects (journal.chestnet.org/article/S0012-…).

8. These results are entirely consistent with the results from in vivo studies: e.g., an 8-month switching study in Apoe-/- mice (PMID: 26609137) and an 18-month dose-response study in A/J mice (PMID: 32780830).

9. In these studies, exposure to THS aerosol did neither lead to significant lung damage (event: “cell/tissue changes”) nor lung function loss (event:” disease”). Switching from cigarettes smoke to THS aerosol exposure yielded results similar to those of cessation. Why?

10. Because THS aerosol did not induce marked changes in inflammatory lung cells (PMID: 26609137, 32780830), and because switching from cigarettes smoke to THS aerosol exposure reduced the number of inflammatory lung cells similarly to cessation (PMID: 26609137). Why?

11. Because THS aerosol did not cause significant biological network perturbations (event: “pert biol mech”) in the lung (PMID: 32780831) and because switching from smoke to THS aerosol exposure reduced all mechanistic perturbations similarly to cessation (PMID: 26609137). Why?

12. Because THS aerosol did not induce changes in lung inflammatory markers (event: “molec chan”) (PMID: 26609137, 32780830) and because switching from cigarettes smoke to THS aerosol exposure reduced the level of inflammatory markers similarly to cessation (PMID: 26609137). Why?

13. Because the animals exposed the THS aerosol showed substantially and significantly lower levels of biomarkers of exposure to toxicants (event: “exposure”), and ...

14. ... importantly, this reduction in exposure is consistent with the reduction in exposure of smokers who switched to THS relative to those who continued to smoke in clinical studies (e.g., PMID: 27816672, 28177489). This reduction achieved 95% of that following cessation. Why?

15. Because THS emits 90-95% lower levels of toxicants than cigarettes (event: “toxic emissions”) (e.g., PMID: 28818540). Why?

16. Because THS heats and does not burn tobacco (sciencedirect.com/science/articl…).

17. All these scientific facts are coherent with the natural law of toxicology, which doesn’t care about our needs or wants, doesn’t care about our opinions and ideologies, our policies and governments, our funding sources and conflicts of interest.

18. #THR is a practical implementation of the natural law of toxicology, with the best option being complete cessation. Yet, ENDPs offer additional opportunities to accelerate the decline of cigarette smoking.

19. For more details, and a broader perspective on ENDPs: elsevier.com/books/toxicolo….

20. Declaration of interest: I joined PMI 13 years ago to work on the scientific assessment of our noncombustible alternatives to cigarettes. I believe that good quality science should drive the #THR dialog and be at the core of policy making.